Transfusion-related iron overload is a major cause of morbidity and mortality in patients with a variety of transfusion- dependant anemias, including sickle cell anemia and thalassemia major. Desferrioxamine (DFO), the current "gold standard" in iron chelation therapy, has been used for over 40 years. Problems include patient non-compliance the phenomenon of rapid filtration into the urine establishing the administered dosage to gram levels. The aim of this proposal is the development of new, more effective formulations of DFO by allowing entrapment of DFO in tissue-targeted liposomes with prolonged circulation times (i.e. pegylated). This will result in a more effective iron chelation using significantly lower DFO dosage. The novel pegylated formulation (peg-LDFO) will undergo complete biodistribution studies, as well as animal test comparisons with free DFO. The optimal formulation developed during Phase 1 will result in a new drug that eventually will significantly reduce patient iron overload, eliminate the need for pump delivery, reduce treatment cost, and increase patient compliance. Phase II will finalize the formulation in preparation for clinical studies. This therapy applies to a category of orphan diseases which typically afflict impoverished and disenfranchised populations;therefore, commercial opportunity is global.